Quinol derivatives as potential trypanocidal agents

Amy Capes, Stephen Patterson, Susan Wyllie, Irene Hallyburton, Iain T. Collie, Andrew J. McCarroll, Malcolm F. G. Stevens, Julie A. Frearson, Paul G. Wyatt, Alan H. Fairlamb, Ian H. Gilbert

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    14 Citations (Scopus)

    Abstract

    Quinols have been developed as a class of potential anti-cancer compounds. They are thought to act as double Michael acceptors, forming two covalent bonds to their target protein(s). Quinols have also been shown to have activity against the parasite Trypanosoma brucei, the causative organism of human African trypanosomiasis, but they demonstrated little selectivity over mammalian MRC5 cells in a counter-screen. In this paper, we report screening of further examples of quinols against T. brucei. We were able to derive an SAR, but the compounds demonstrated little selectivity over MRC5 cells. In an approach to increase selectivity, we attached melamine and benzamidine motifs to the quinols, because these moieties are known to be selectively concentrated in the parasite by transporter proteins. In general these transporter motif-containing analogues showed increased selectivity; however they also showed reduced levels of potency against T. brucei. (C) 2011 Elsevier Ltd. All rights reserved.

    Original languageEnglish
    Pages (from-to)1607-1615
    Number of pages9
    JournalBioorganic & Medicinal Chemistry
    Volume20
    Issue number4
    DOIs
    Publication statusPublished - 15 Feb 2012

    Keywords

    • Inhibitors
    • Medicinal chemistry
    • Trypanosoma brucei
    • P2 transporter
    • Quinols
    • HUMAN AFRICAN TRYPANOSOMIASIS
    • CANCER CELL-LINES
    • THERAPEUTIC AGENTS
    • ANTITUMOR QUINOLS
    • BRUCEI
    • THIOREDOXIN
    • BENZOTHIAZOLE
    • APOPTOSIS
    • TARGET
    • CYCLOADDITIONS

    Cite this

    Capes, A., Patterson, S., Wyllie, S., Hallyburton, I., Collie, I. T., McCarroll, A. J., Stevens, M. F. G., Frearson, J. A., Wyatt, P. G., Fairlamb, A. H., & Gilbert, I. H. (2012). Quinol derivatives as potential trypanocidal agents. Bioorganic & Medicinal Chemistry, 20(4), 1607-1615. https://doi.org/10.1016/j.bmc.2011.12.018